CN110028430B - Preparation method of sulindac - Google Patents
Preparation method of sulindac Download PDFInfo
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- CN110028430B CN110028430B CN201910439438.2A CN201910439438A CN110028430B CN 110028430 B CN110028430 B CN 110028430B CN 201910439438 A CN201910439438 A CN 201910439438A CN 110028430 B CN110028430 B CN 110028430B
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
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- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
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Abstract
The invention relates to the technical field of drug synthesis, and particularly relates to a preparation method of sulindac. The preparation method provided by the invention comprises the following steps: mixing 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, a photosensitizer, an oxidant and a reaction solvent, and carrying out oxidation reaction under the condition of ultraviolet irradiation to obtain sulindac; wherein, the 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid comprises an E-type isomer and a Z-type isomer. The method provided by the invention directly uses 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid containing E-type isomers and Z-type isomers as a raw material to obtain the sulindac through oxidation reaction, does not need to separate and purify the sulindac, and is simple to operate. The experimental results of the embodiment show that the method for preparing sulindac has the advantages of high yield of 98.9% and purity of more than 99.5%.
Description
Technical Field
The invention relates to the technical field of drug synthesis, and particularly relates to a preparation method of sulindac.
Background
Sulindac is a non-steroidal anti-inflammatory drug mainly used for treating pain, rheumatoid arthritis, lumbago and gouty arthritis, and is also used for treating premature delivery and diabetic senile cataract. In recent years, the application of sulindac in tumor treatment is receiving the attention of researchers, and many researches show that sulindac has the capacity of inhibiting the growth of tumor cells, so that the research of products of the type draws more extensive attention of the world scientific community and the public opinion community.
In the synthetic method of sulindac reported in the prior literature and patent, 5-fluoro-2-methyl-3-indene acetic acid is mainly obtained by reacting 5-fluoro-2-methyl-3-indene acetic acid with p-methylthiobenzaldehyde, the main configuration of the obtained 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is Z type, but the E type isomer is about 10% at the same time, since the target product sulindac is Z-5-fluoro-2-methyl-1- (4-methylsulfinylbenzylidene) -3-indene acetic acid, the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) acetic acid obtained in the prior art is usually treated first Recrystallizing the 3-indene acetic acid to obtain the Z-type isomer (E-type isomer is in mother liquor) of the 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, and then carrying out oxidation reaction to obtain the sulindac. Since the E-isomer of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid can be partially converted into the Z-isomer under certain conditions, in the actual process, in order to improve the yield of sulindac, 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid usually needs to be recrystallized and reacted for many times, and the operation is complicated.
Disclosure of Invention
The invention aims to provide a preparation method of sulindac, which directly takes 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid comprising an E-type isomer and a Z-type isomer as a raw material to obtain the sulindac through oxidation reaction, does not need to carry out repeated recrystallization and reaction conversion on the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid, and is simple to operate.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of sulindac, which comprises the following steps:
mixing 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, a photosensitizer, an oxidant and a reaction solvent, and carrying out oxidation reaction under the condition of ultraviolet irradiation to obtain sulindac;
wherein, the 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid comprises an E-type isomer and a Z-type isomer.
Preferably, the photosensitizer comprises acetophenone, anthracene, benzophenone, or benzoin dimethyl ether.
Preferably, the oxidant comprises hydrogen peroxide, peracetic acid or m-chloroperoxybenzoic acid.
Preferably, the reaction solvent comprises one or more of ethyl acetate, chloroform, toluene, dichloromethane and ethanol.
Preferably, the molar ratio of the oxidant to the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is (1-1.1): 1; the mass ratio of the photosensitizer to the reaction solvent to the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is (0.01-0.1): (5-15): 1.
preferably, the wavelength range of the ultraviolet light is 315-400 nm.
Preferably, the temperature of the oxidation reaction is 10-80 ℃ and the time is 3-12 h.
Preferably, the oxidation reaction further comprises recrystallization, and the reagent for recrystallization comprises methanol, ethanol or isopropanol.
Preferably, when the reaction solvent is the same as the reagent for recrystallization, the method for recrystallization includes:
removing part of reaction solvent in the system obtained after the oxidation reaction, then recrystallizing, and carrying out solid-liquid separation on the obtained material to obtain the sulindac.
Preferably, when the reaction solvent is not the same as the reagent for recrystallization, the method for recrystallization includes:
and removing the reaction solvent in the system obtained after the oxidation reaction, dissolving the remainder in a reagent for recrystallization, then recrystallizing, and carrying out solid-liquid separation on the obtained material to obtain the sulindac.
The invention provides a preparation method of sulindac, which comprises the following steps: mixing 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, a photosensitizer, an oxidant and a reaction solvent, and carrying out oxidation reaction under the condition of ultraviolet irradiation to obtain sulindac; wherein, the 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid comprises an E-type isomer and a Z-type isomer. The method provided by the invention directly uses 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid containing E-type isomer and Z-type isomer as a raw material, absorbs photons through a photosensitizer under the condition of ultraviolet irradiation, then transfers energy into the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid to realize the inversion of the double bond configuration of the E-type isomer, and utilizes an oxidant to carry out oxidation reaction on the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid to finally obtain sulindac, so that the raw material 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid does not need to be subjected to separation and purification such as recrystallization, reaction and conversion and the like The reaction can be directly carried out, the process is simple and convenient, and the operation is simple. The experimental results of the embodiment show that the method for preparing sulindac has the advantages of high yield of 98.9% and purity of more than 99.5%.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of the product prepared in example 1.
Detailed Description
The invention provides a preparation method of sulindac, which comprises the following steps:
mixing 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, a photosensitizer, an oxidant and a reaction solvent, and carrying out oxidation reaction under the condition of ultraviolet irradiation to obtain sulindac;
wherein, the 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid comprises an E-type isomer and a Z-type isomer.
According to the preparation method of sulindac provided by the invention, 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid containing E-type isomers and Z-type isomers is directly used as a raw material to obtain sulindac through oxidation reaction, repeated recrystallization and reaction transformation of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid (compound II) are not needed, and the operation is simple. In the invention, the proportion of the Z-type isomer in the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is preferably 50-92%. The source of the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is not particularly limited in the present invention, and the 5-fluoro-2-methyl-3-indene acetic acid can be prepared by a method well known to those skilled in the art, specifically, 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is obtained by reacting 5-fluoro-2-methyl-3-indene acetic acid with p-methylthiobenzaldehyde, about 90% of the Z-isomer in the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid obtained by the method, and the Z-isomer and the mother crystal of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid can be obtained by recrystallization The content of E-type isomer is not changed in the recrystallization process of the mother liquor, and after 2 times of recrystallization, the proportion of Z-type isomer of 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid in the mother liquor is about 50 percent. The method provided by the invention can be used for preparing sulindac by directly using the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid obtained by the method as a raw material, and can also be used for preparing sulindac by using the mother liquor after 1-2 times of recrystallization, so that repeated recrystallization and reaction conversion of the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid are not needed, and the operation is simple.
In the present invention, the photosensitizer preferably includes acetophenone, anthracene, benzophenone, or benzoin dimethyl ether; the oxidant preferably comprises hydrogen peroxide, peracetic acid or m-chloroperoxybenzoic acid; the reaction solvent preferably comprises one or more of ethyl acetate, chloroform, toluene, dichloromethane and ethanol, and more preferably ethyl acetate, chloroform, toluene, dichloromethane, ethanol, an ethyl acetate-chloroform mixture or a dichloromethane-ethanol mixture; when the reaction solvent is a mixture of more than two solvents, the proportion of each solvent is not particularly limited, and any proportion can be adopted.
In the invention, the molar ratio of the oxidant to the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is preferably (1-1.1): 1; the mass ratio of the photosensitizer to the reaction solvent to the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is preferably (0.01-0.1): (5-15): 1.
the invention has no special limitation on the feeding sequence and the mixing mode when the 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, the photosensitizer, the oxidant and the reaction solvent are mixed, and all the components can be uniformly mixed.
After 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, a photosensitizer, an oxidant and a reaction solvent are mixed, the obtained mixed material is subjected to oxidation reaction under the condition of ultraviolet irradiation, and sulindac is obtained. In the invention, the wavelength range of the ultraviolet light is preferably 315-400 nm. In the invention, the temperature of the oxidation reaction is preferably 10-80 ℃, more preferably 20-40 ℃, and further preferably 25-30 ℃; the time is preferably 3 to 12 hours, more preferably 3 to 8 hours, and further preferably 4 to 6 hours. In the invention, the oxidation reaction is preferably carried out under the condition of stirring, and the stirring speed is preferably 200-400 r/min, and more preferably 250-350 r/min. In the present invention, the oxidation reaction is preferably carried out in a reaction vessel equipped with a thermometer, a stirrer and an ultraviolet light source.
In the present invention, it is preferable that the oxidation reaction is further followed by recrystallization, and the recrystallization reagent includes methanol, ethanol, or isopropanol, and more preferably ethanol.
In the present invention, when the reaction solvent is the same as the reagent for recrystallization, the method for recrystallization preferably includes: removing part of reaction solvent in the system obtained after the oxidation reaction, then recrystallizing, and carrying out solid-liquid separation on the obtained material to obtain the sulindac.
In the present invention, when the reaction solvent is the same as the recrystallization reagent, after the oxidation reaction is completed, part of the reaction solvent in the resulting system is removed, and the remaining organic solvent can be used as the recrystallization reagent for the subsequent recrystallization treatment. The method for removing the part of the reaction solvent in the present invention is not particularly limited, and may be a method known to those skilled in the art, such as rotary evaporation. The invention has no special limit on the amount of the partial reaction solvent, and can ensure that the subsequent recrystallization can be carried out smoothly. In the invention, the recrystallization temperature is preferably 5-10 ℃, and more preferably 10 ℃. The solid-liquid separation method is not particularly limited, and a method known to those skilled in the art, such as filtration, may be used.
In the present invention, when the reaction solvent is not the same as the reagent for recrystallization, the method for recrystallization preferably includes: and removing the reaction solvent in the system obtained after the oxidation reaction, dissolving the remainder in a reagent for recrystallization, then recrystallizing, and carrying out solid-liquid separation on the obtained material to obtain the sulindac.
In the present invention, when the reaction solvent is different from the recrystallization reagent, in order to ensure the recrystallization effect, it is necessary to remove all the reaction solvent in the system obtained after the oxidation reaction, dissolve the remainder in the recrystallization reagent, and then perform recrystallization. The method for removing the reaction solvent in the present invention is not particularly limited, and may be a method known to those skilled in the art, such as rotary evaporation. In the invention, the recrystallization temperature is preferably 5-10 ℃, and more preferably 10 ℃. The solid-liquid separation method is not particularly limited, and a method known to those skilled in the art, such as filtration, may be used.
In the invention, the reaction formula for preparing sulindac by using 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid as a raw material is shown as follows:
in the reaction formula, the compound II is 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, and a wavy line in the structural formula of the compound II represents that the compound comprises an E-type isomer and a Z-type isomer; the compound I refers to sulindac and has the chemical name of Z-5-fluoro-2-methyl-1- (4-methanesulfonamidobenzylidene) -3-indene acetic acid.
Under the condition of ultraviolet irradiation, the photosensitizer absorbs photons, then energy is transferred into a reaction substrate (namely 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid), the inversion of the E-type isomer double bond configuration is realized, meanwhile, an oxidant is utilized to carry out oxidation reaction on the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid, and sulindac is finally obtained, so that the raw material 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid can directly react without separation and purification treatment such as recrystallization, reaction conversion and the like, the process is simple and convenient, and the operation is simple.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Adding 25g of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid (Z: E ═ 66: 33), 5.6g of peroxyacetic acid, 0.5g of anthracene and 300g of ethanol into a 1L reaction vessel provided with a thermometer, a stirrer and an ultraviolet light source (the wavelength range is 315-400 nm), and reacting for 5 hours at 25 ℃ and 300r/min under the ultraviolet irradiation condition; after the reaction is finished, 250g of ethanol is evaporated from the obtained system, the obtained system is cooled to 10 ℃ for recrystallization, and the obtained product is subjected to suction filtration to obtain 25.5g of sulindac, wherein the yield is 97.4 percent, and the purity is more than 99.5 percent.
Fig. 1 is a nuclear magnetic hydrogen spectrum of the product prepared in this example, and the data is specifically as follows:
1HNMR(500MHz,CDCl3)δ7.71(d,J＝8.2Hz,2H),7.63(d,J＝8.2Hz,2H),7.14(s,1H),7.11(dd,J＝8.4,5.1Hz,1H),6.88(dd,J＝8.8,2.3Hz,1H),6.54(td,J＝8.9,2.3Hz,1H),3.58(s,2H),2.83(s,3H),2.20(s,3H).
from figure 1 and the above data, it can be seen that the product prepared in this example is indeed sulindac.
Example 2
Adding 25g of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid (Z: E ═ 66: 33), 6.15g of peroxyacetic acid, 0.5g of anthracene and 375g of toluene into a 1L reaction vessel provided with a thermometer, a stirrer and an ultraviolet light source (the wavelength range is 315-400 nm), and reacting at 10 ℃ and 300r/min for 12 hours under the condition of ultraviolet irradiation; and after the reaction is finished, evaporating the obtained system to dryness, dissolving the residue in 50g of ethanol, cooling to 10 ℃, recrystallizing and filtering to obtain 25.9g of sulindac, wherein the yield is 98.9%, and the purity is more than 99.0%.
Example 3
Adding 25g of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid (Z: E: 50), 12.7g of m-chloroperoxybenzoic acid, 0.5g of acetophenone, 50g of ethyl acetate and 75g of chloroform into a 1L reaction vessel provided with a thermometer, a stirrer and an ultraviolet light source (the wavelength range is 315-400 nm), and reacting at 80 ℃ and 300r/min for 3h under the ultraviolet irradiation condition; and after the reaction is finished, evaporating the obtained system to dryness, dissolving the residue in 50g of ethanol, cooling to 10 ℃, recrystallizing and filtering to obtain 24.9g of sulindac, wherein the yield is 95.1%, and the purity is more than 99.5%.
Example 4
Adding 25g of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid (Z: E: 90: 10), 8.33g of hydrogen peroxide with the mass concentration of 30%, 0.25g of benzoin dimethyl ether, 200g of ethanol and 100g of dichloromethane into a 1L reaction vessel provided with a thermometer, a stirrer and an ultraviolet light source (the wavelength range is 315-400 nm), and reacting for 5 hours at 25 ℃ and 300r/min under the ultraviolet irradiation condition; and after the reaction is finished, evaporating the obtained system to dryness, dissolving the residue in 50g of ethanol, cooling to 10 ℃, recrystallizing and filtering to obtain 25.5g of sulindac, wherein the yield is 97.4%, and the purity is more than 99.5%.
Example 5
Adding 25g of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid (Z: E: 92: 8), 8.33g of hydrogen peroxide with the mass concentration of 30%, 2.5g of benzophenone and 300g of ethanol into a 1L reaction vessel provided with a thermometer, a stirrer and an ultraviolet light source (the wavelength range is 315-400 nm), and reacting for 5 hours at 25 ℃ and 300r/min under the ultraviolet irradiation condition; after the reaction is finished, 250g of ethanol is evaporated from the obtained system, the obtained system is cooled to 10 ℃ for recrystallization, and the obtained product is subjected to suction filtration to obtain 25.5g of sulindac, wherein the yield is 97.4 percent, and the purity is more than 99.5 percent.
Example 6
Adding 25g of 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid (Z: E ═ 66: 33), 5.6g of peroxyacetic acid, 0.5g of anthracene and 300g of toluene into a 1L reaction vessel provided with a thermometer, a stirrer and an ultraviolet light source (wavelength range is 315-400 nm), and reacting for 5 hours at 30 ℃ and 300r/min under the condition of ultraviolet irradiation; and after the reaction is finished, evaporating the obtained system to dryness, dissolving the residue in 50g of ethanol, cooling to 10 ℃, recrystallizing and filtering to obtain 25.9g of sulindac, wherein the yield is 98.9%, and the purity is more than 99.5%.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (8)
1. A preparation method of sulindac is characterized by comprising the following steps:
mixing 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid, a photosensitizer, an oxidant and a reaction solvent, and carrying out oxidation reaction under the condition of ultraviolet irradiation to obtain sulindac; the photosensitizer is acetophenone, anthracene, benzophenone or benzoin dimethyl ether; the oxidant is hydrogen peroxide, peroxyacetic acid or m-chloroperoxybenzoic acid;
wherein, the 5-fluoro-2-methyl-1- (4-methylthio-benzylidene) -3-indene acetic acid comprises an E-type isomer and a Z-type isomer.
2. The method according to claim 1, wherein the reaction solvent comprises one or more of ethyl acetate, chloroform, toluene, dichloromethane, and ethanol.
3. The method according to any one of claims 1 to 2, wherein the molar ratio of the oxidizing agent to 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is (1 to 1.1): 1; the mass ratio of the photosensitizer to the reaction solvent to the 5-fluoro-2-methyl-1- (4-methylthiobenzylidene) -3-indene acetic acid is (0.01-0.1): (5-15): 1.
4. the method according to claim 3, wherein the ultraviolet light has a wavelength of 315 to 400 nm.
5. The preparation method according to claim 4, wherein the temperature of the oxidation reaction is 10-80 ℃ and the time is 3-12 h.
6. The method according to claim 1 or 5, wherein the oxidation reaction is followed by recrystallization, and the recrystallization reagent comprises methanol, ethanol, or isopropanol.
7. The production method according to claim 6, wherein when the reaction solvent is the same as the reagent for recrystallization, the method for recrystallization comprises:
removing part of reaction solvent in the system obtained after the oxidation reaction, then recrystallizing, and carrying out solid-liquid separation on the obtained material to obtain the sulindac.
8. The method according to claim 6, wherein when the reaction solvent is different from the recrystallization reagent, the recrystallization method comprises:
and removing the reaction solvent in the system obtained after the oxidation reaction, dissolving the remainder in a reagent for recrystallization, then recrystallizing, and carrying out solid-liquid separation on the obtained material to obtain the sulindac.
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Citations (3)
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| US3692651A (en) * | 1970-05-01 | 1972-09-19 | Meyer Sletzinger | Process for preparing cis 5-fluoro-2-methyl - 1 - (p-methylsulfinylbenzylidene)-3-indenyl acetic acid |
| CN102115452A (en) * | 2009-12-30 | 2011-07-06 | 上海特化医药科技有限公司 | (E)-3-(3-substituted-5-methylphenyl)acrylonitrile and preparation method thereof |
| CN104073286A (en) * | 2014-07-17 | 2014-10-01 | 江苏大学 | Method for removing sulfides in fuel oil through photo oxidation |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3692651A (en) * | 1970-05-01 | 1972-09-19 | Meyer Sletzinger | Process for preparing cis 5-fluoro-2-methyl - 1 - (p-methylsulfinylbenzylidene)-3-indenyl acetic acid |
| CN102115452A (en) * | 2009-12-30 | 2011-07-06 | 上海特化医药科技有限公司 | (E)-3-(3-substituted-5-methylphenyl)acrylonitrile and preparation method thereof |
| CN104073286A (en) * | 2014-07-17 | 2014-10-01 | 江苏大学 | Method for removing sulfides in fuel oil through photo oxidation |
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